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Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 proliferative LN patients to either cyclophosphamide pulses (750 mg/m(2), 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2 mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 x 3 pulses of 1000 mg) and oral prednisone (AZA). After a median follow-up of 5.7 years (interquartile range 4.1-7.2 years), doubling of serum creatinine was more frequent in the AZA group, although not statistically significant (relative risk (RR): 4.1, with 95% confidence interval (95% CI): 0.8-20.4). Relapses occurred more often in the AZA group (RR: 8.8, 95% CI: 1.5-31.8). Creatinine and proteinuria at last visit did not differ between the two treatment arms. Moreover, 88.4% of the patients in the AZA arm were still free of cyclophosphamide treatment. During the first 2 years, the frequency of remission was not different, but infections, especially herpes zoster virus infections (HZV) were more frequent in the AZA group. Parameters for ovarian function did not differ between the two groups. In conclusion, in this open-label randomized controlled trial, cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV. At last follow-up, there were no differences in serum creatinine or proteinuria between the two groups. However, since our study lacked sufficient power, longer follow-up is needed to reveal putative differences.

Reliable and sensitive measures are needed to evaluate the quality of life (QoL) in patients with systemic lupus erythematosus (SLE). No lupus specific questionnaires are available. This study describes the development and validation of a disease-specific questionnaire for lupus patients, which assesses the presence and burden of 38 disease- and treatment-related symptoms: the SLE Symptom Checklist (SSC). Reliability and reproducibility were tested in respectively 87 and 28 stable SLE patients. The internal consistency (Cronbach's alpha coefficients 0.89) and test-retest reliability (Pearson product-moment correlation coefficient between 0.67 and 0.87) were satisfactory. Concurrent validity was supported by significant, but moderate correlations with other measures of subjective well-being and functional status. Responsiveness was measured in 17 patients with lupus nephritis treated with cyclophosphamide, at start of therapy and 1 year thereafter. A significant change in number of symptoms and total distress level was found. It is concluded that the SSC has satisfactory psychometric properties and appears suitable for both clinical and research purposes.

Objective: To evaluate the treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine., Patients and Methods: Eighteen patients with severe proliferative lupus nephritis (Class III, IV or Vd according to criteria of the World Health Organization) were treated with intravenous methylprednisolone (MP) pulse therapy in combination with a low oral maintenance dose of prednisone (20 mg) and azathioprine (2 mg/kg). Thirteen patients (Group I) had a recent onset of clinical manifestations of nephritis at referral (mean and median 4 months). Five patients (Group II) had clinical signs of nephritis for a long time (median 4 years, mean 5 years) and were referred because of progressive renal failure. The mean plasma creatinine in Group I was 109 mumol/l with a mean GFR of 58 ml/min, the mean plasma creatinine in Group II was 284 mumol/l with a mean GFR of 12 ml/min. Renal histology in Group II was characterized by severe chronic damage (chronicity index 8-10)., Results: Short-term and long-term effects of treatment were excellent in Group I. The mean plasma creatinine was 68 mumol/l with a mean GFR of 102 ml/min at a mean follow-up of 7 years, median 4 years (range 1-15 years). All patients in Group II needed renal replacement therapy after a mean follow-up of 2.6 years, median 2 years (range 0-8 years). Major side-effects of treatment were only seen twice., Conclusion: Methylprednisolone pulse therapy in combination with low oral maintenance doses of prednisone and oral azathioprine is an effective and safe treatment for patients with severe active proliferative lupus nephritis. In patients with extensive irreversible lesions, this treatment has no or only a temporary effect.

Proliferative glomerulonephritis is a severe clinical manifestation of systemic lupus erythematosus, and it remains a major determinant of morbidity and mortality in this disease, despite the progress that has been made by treating patients with a combination of corticosteroids and cytotoxic drugs. Earlier controlled clinical trials have demonstrated the superior efficacy of a combination of pulse cyclophosphamide with steroids over treatment with steroids alone. However, cyclophosphamide carries a substantial risk of short-term and long-term toxicity in this predominantly young population, and previous trials have not convincingly shown any benefit over the milder treatment with a combination of azathioprine and steroids. We propose to conduct a Dutch multicentre trial to test whether similar renal survival can be achieved with an azathioprine-based regimen, compared to the widely used cyclophosphamide treatment, with a possibly lower risk of adverse effects.

Twenty-five patients with rapidly progressive glomerulonephritis (RPGN) were treated with methylprednisolone (MP) pulse therapy (1 g intravenously on 3 successive days). In all patients renal biopsy was done before or just after the start of therapy. Pulse therapy was used in all patients in combination with a low oral maintenance dose of prednisone. In 21 patients additional immunosuppressive treatment was given, either cyclophosphamide (n = 19) or azathioprine (n = 2); in 2 patients plasmapheresis was also applied. Sixteen of the 25 patients were dialysis-dependent at presentation; 11 of them improved, an additional 3 had a temporary recovery, but needed maintenance renal replacement therapy after 5-46 months, mean 22 months. Nine of the 25 patients were not dialysis-dependent, 6 of them improved, an additional one had a temporary recovery, but needed chronic dialysis after 35 months. When many irreversible glomerular lesions were present, the effectiveness of MP pulse therapy was limited or only of a temporary character. Serious side effects did not occur. In conclusion MP pulse therapy is a successful treatment with minimal adverse reactions in patients with RPGN and active histological lesions.

A 30-year-old woman, who in the past was diagnosed as having systemic lupus erythematosus (SLE) and had been treated accordingly, consulted us with neuropsychiatric symptoms, including mutism and catatonia. ANA and anti-dsDNA in serum were negative, and she did not fulfill the ARA criteria for a diagnosis of SLE. However, in view of her history and the fact that she developed convulsions and a transient, unexplained period of leukopenia during admission, her current illness could be interpreted as a cerebral manifestation of SLE. After increasing the dosage of prednisone, she recovered almost completely from this episode. The literature concerning possible procedures to diagnose neuropsychiatric manifestations of SLE is reviewed; it turns out that especially the primary form of cerebral SLE often causes diagnostic problems.